Biological evaluation of two anomeric glucose analogues iodinated in position 6

Two anomeric analogues of glucose labelled with 123 iodine in position 6, proposed as tracers of glucose transport in vivo, have been synthesized: alpha- and beta-methyl-6-deoxy-6-iodo-D-glucopyranoside (alpha MDIG and beta MDIG). The aim of this study was to determine whether these molecules interact with the glucose transporter and whether they could be used as tracers of glucose transport in vivo. The biodistribution of alpha MDIG and beta MDIG was studied in the mouse in vivo. To determine if these two anomers enter the cell via the glucose transporter, their uptake was measured in isolated perfused rat hearts, in human erythrocytes in suspension, and in cardiomyocytes of neonatal rat in culture. Both alpha MDIG and beta MDIG had similar repartitions in the mouse: myocardial uptake averaged 7% of the injected dose/g of organ at 2 min postinjection and alpha MDIG competed with D-glucose to enter the cells. Insulin produced a 123% increase of its uptake in isolated perfused rat hearts and a 100% increase in cardiomyocytes of neonatal rat in culture. alpha MDIG uptake was lowered in the presence of glucose transport inhibitors in each experimental model. An interaction between beta MDIG and glucose transporters was observed only in human erythrocytes in suspension. Only alpha MDIG interacts with the glucose transporter, and thus could be used to estimate glucose transport in vivo.     

Metastatic renal cell carcinoma presenting as an aural polyp

Renal cell carcinoma may metastasize to the head and neck region at different stages of its evolution. We present a case of an undiagnosed renal cell carcinoma presenting as an ear polyp, and discuss the difficulties of the diagnosis and the management of these tumours.     

Macroscopic and crystallographic density of solid-state extruded polyethylene

Summary The influence of draw ratio on macroscopic and crystallographic density of polyethylene with different initial morphologies, has been investigated by solid-state extrusion. An initial drop followed by an increase in macroscopic density as a function of draw ratio has been observed. Since precision X-ray measurements of unit cell parameters showed no variation of crystallographic density, it was concluded that plastic deformation of polyethylene upon drawing proceeds with a decrease of the degree of crystallinity. This was confirmed by differential scanning calorimetry.     

Ganglioside content of human platelets--differences in resting and activated platelets

Gangliosides may play functional roles in platelet physiology, therefore this study has been designed to evaluate whether changes in ganglioside composition may occur as a consequence of platelet activation. The results obtained indicate that lactosylceramide and GM3 are the major glycosphingolipids of human platelets. The lipid-bound sialic acid (LBSA) content was 1.27 +/- 0.04 micrograms/mg of protein. Resting platelets did not express GD3; GD3 was synthesized upon platelet activation (24 +/- 8 ng/mg of protein). The stimulation of platelets with adenosine diphosphate showed the appearance of GD3 even in the absence of degranulation. Finally, incorporation of pyrene-labeled GM3 into platelet membranes, followed by stimulation with adenosine diphosphate, resulted in the appearance of a fluorescent band comigrating with GD3. The present studies indicate that sialytransferase activation may occur as an early event following platelet stimulation, leading to GD3 synthesis mainly from the GM3 pool.     

Dependence on the motif YIPP for the physical association of Jak2 kinase with the intracellular carboxyl tail of the angiotensin II AT1 receptor

Angiotensin II is the effector molecule of the renin-angiotensin system. Virtually all of its biochemical actions are mediated through a single class of cell-surface receptors called AT1. These receptors contain the structural features of the seven-transmembrane, G-protein-coupled receptor superfamily. Angiotensin II, acting through the AT1 receptor, also stimulates the Jak/STAT pathway by inducing ligand-dependent Jak2 tyrosine phosphorylation and activation. Here, we show that a glutathione S-transferase fusion protein containing the carboxyl-terminal 54 amino acids of the rat AT1A receptor physically binds to Jak2 in an angiotensin II-dependent manner. Deletional analysis, using both in vitro protocols and cell transfection analysis, showed that this association is dependent on the AT1A receptor motif YIPP (amino acids 319-322). The wild-type AT1A receptor can induce Jak2 tyrosine phosphorylation. In contrast, an AT1A receptor lacking the YIPP motif is unable to induce ligand-dependent phosphorylation of Jak2. Competition experiments with synthetic peptides suggest that each of the YIPP amino acids, including tyrosine 319, is important in Jak2 binding to the AT1A receptor. The binding of the AT1A receptor to the intracellular tyrosine kinase Jak2 supports the concept that the seven-transmembrane superfamily of receptors can physically associate with enzymatically active intracellular proteins, creating a signaling complex mechanistically similar to that observed with growth factor and cytokine receptors.     

Arthroscopic lysis in knee arthrofibrosis

OBJECTIVE: To compare the efficacy and toxicity of three patient-controlled analgesia (PCA) morphine regimens. DESIGN: A prospective, randomized, pilot study of three PCA morphine regimens: (1) 1 mg with 6-minute lockout (n = 10), (2) 2 mg with 12-minute lockout (n = 12), and (3) 2 mg with 20-minute lockout (n = 12). SETTING: Large teaching institution. PARTICIPANTS: Thirty-four patients undergoing cholecystectomy or hysterectomy. MAIN OUTCOME MEASURES: Pain scores (0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = severe pain), sedation scores, analgesic consumption, and patient attempts (patient activation of PCA device) and injections (doses actually delivered) were evaluated using analysis of covariance. Distribution of pain and sedation scores and adverse effects were assessed using Fisher's exact test. RESULTS: Data on 24 patients were evaluable. Six patients withdrew for poor pain control (2 in group 1, 1 in group 2, and 3 in group 3). Three other patients withdrew because of adverse effects and 1 withdrew because of pump problems. Mean morphine consumption did not differ significantly among the groups. Distribution of pain and sedation scores and the number of patients with nausea were similar across treatment groups. The mean injection to attempt ratio was significantly smaller in group 3 (0.71 +/- 0.11) compared with groups 1 and 2 (0.9 +/- 0.06 and 0.83 +/- 0.09, respectively; p = 0.001). Adverse events occurred similarly among treatment groups. CONCLUSIONS: No significant differences in the efficacy or toxicity of the three morphine PCA regimens were identified.     

VRCTC-310--a novel compound of purified animal toxins separates antitumor efficacy from neurotoxicity

Two purified animal venom toxins, crotoxin and cardiotoxin, have been combined to produce a unique natural product (VRCTC-310) currently under investigation as an antitumor agent by the National Cancer Institute. In vitro, it has demonstrated cytotoxic disease specificity and a unique mechanism of action when submitted to COMPARE analysis. In vivo, tolerance was developed to the neurotoxic properties of crotoxin which allowed comparison of several schedules of fixed and escalating daily i.m. doses to mice bearing s.c. Lewis Lung carcinoma. An 83% inhibition of tumor growth was achieved using an escalating dose schedule starting at 1.8 mg/kg and reaching 6.3 mg/kg/day on day 20. Although some irritation around the sites of i.m. injection was noted, animal weight loss was negligible and there were no other signs of adverse toxicity. This natural product represents a new, membrane interactive anticancer agent which produces a unique spectrum of cytotoxicity in vitro and which has demonstrated interesting in vivo antitumor efficacy.     

Estimating eye care workforce supply and requirements

PURPOSE: To estimate the workforce supply and requirements for eye care in the United States. METHODS: Three models were constructed for analysis: supply of providers, public health need for eye care, and demand (utilization) for eye care. Ophthalmologists, other physicians, and optometrists were included in the models. Public health need was determined by applying condition-specific prevalence and incidence rates from population-based and other epidemiologic studies. Demand was determined by use of national databases, such as the National Ambulatory Care Survey, National Hospital Discharge Survey, and Medicare Part B. Time requirements for care were obtained through a stratified sample survey of the membership of the American Academy of Ophthalmology. RESULTS: Under modeling assumptions that use a work-time ratio of one between optometrists and ophthalmologists and between specialist and generalist ophthalmologists, a significant excess of eye care providers exists relative to both public health need and demand. Changes in the work-time ratio, work-hours per year per provider, care patterns for the same condition, or other factors could significantly reduce or eliminate the surplus relative to need. CONCLUSION: If optometrists are the preferred primary eye care provider, ophthalmologists would be in excess under all demand scenarios and all need scenarios where the optometrist to ophthalmologist work-time ratio is greater than 0.6. No excess of ophthalmologists would exist if ophthalmologists are the preferred primary eye care provider. Data on the appropriate work time ratio will help refine estimates of the imbalance between supply and requirements.     

Cost-effective smart power CMOS/DMOS technology: design methodology for latch-up immunity

To answer to the need of a cost effective smart power technology, an original design methodology that permits implementing latch-up free smart power circuits on a very simple CMOS/DMOS technology is proposed. The basic concept used to this purpose is letting float the wells of the MOS transistors most susceptible to initiate latch-up. The efficiency of the design methodology is experimentally shown.